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BackgroundThis meta-analysis investigated the influence of exercise on cognitive function in people living with diabetes.MethodsStringent criteria for literature inclusion and exclusion were defined. Searches were conducted across four English databases to gather randomized controlled trials investigating exercise interventions for cognitive function in people living with diabetes. Outcome indicators from 1193 subjects across 12 articles were analyzed using RevMan 5.4 software.ResultsExercise intervention demonstrated the ability to mitigate cognitive decline in people living with diabetes, with a combined effect size (standardized mean difference) of 0.91, 95% CI: 0.28, 1.54, P < 0.00001. The intervention effect showed significant modulation by intervention content (I2 = 95%), intervention duration (I2 = 95%), intervention frequency (I2 = 95%), and intervention cycle (I2 = 96%). Among these factors, multi-component exercise, sessions >40 minutes, exercise frequency >4 times per week, and sustained exercise for >6 months were paramount, all with P < 0.05.ConclusionExercise intervention emerges as a viable strategy for delaying cognitive decline in people living with diabetes. Its efficacy is subject to modulation by various variables. Optimal intervention includes multi-component exercise, individual sessions lasting 40-60 minutes, exercising >4 times a week, and continuous exercise for over 6 months.

Neutrophils play a critical role in host defense against Pseudomonas aeruginosa infection. Mechanisms underlying the negative regulation of neutrophil function in bacterial clearance remain incompletely defined. Here, we demonstrate that protein tyrosine phosphatase-1B (PTP1B) is a negative regulator of P. aeruginosa clearance by neutrophils. PTP1B-deficient neutrophils display greatly enhanced bacterial phagocytosis and killing, which are accompanied by increased Toll-like receptor 4 (TLR4) signaling activation and nitric oxide (NO) production following P. aeruginosa infection. Interestingly, PTP1B deficiency mainly upregulates the production of IL-6 and IFN-β, leads to enhanced TLR4-dependent STAT1 activation and iNOS expression by neutrophils following P. aeruginosa infection. Further studies reveal that PTP1B and STAT1 are physically associated. These findings demonstrate a negative regulatory mechanism in neutrophil underlying the elimination of P. aeruginosa infection though a PTP1B-STAT1 interaction.

Stroke is a devastating and potentially preventable complication of cardiac surgery. Tranexamic acid (TXA) is a commonly antifibrinolytic agent in cardiac surgeries with cardiopulmonary bypass (CPB), however, there is concern that it might increase incidence of stroke after cardiac surgery. In this retrospective study, we investigated whether TXA usage could increase postoperative stroke in cardiac surgery.A retrospective study was conducted from January 1, 2010, to December 31, 2015, in 2,016 patients undergoing cardiac surgery, 664 patients received intravenous TXA infusion and 1,352 patients did not receive any antifibrinolytic agent. Univariate and propensity-weighted multivariate regression analysis were applied for data analysis.Intraoperative TXA administration was associated with postoperative stroke (1.7% vs. 0.5%; adjusted OR, 4.11; 95% CI, 1.33 to 12.71; p = 0.014) and coma (adjusted OR, 2.77; 95% CI, 1.06 to 7.26; p = 0.038) in cardiac surgery. As subtype analysis was performed, TXA administration was still associated with postoperative stroke (1.7% vs. 0.3%; adjusted OR, 5.78; 95% CI, 1.34 to 27.89; p = 0.018) in patients undergoing valve surgery or multi-valve surgery only, but was not associated with postoperative stroke (1.7% vs. 1.3%; adjusted OR, 5.21; 95% CI, 0.27 to 101.17; p = 0.276) in patients undergoing CABG surgery only. However, TXA administration was not associated with postoperative mortality (adjusted OR, 1.31; 95% CI, 0.56 to 3.71; p = 0.451), seizure (adjusted OR, 1.13; 95% CI, 0.42 to 3.04; p = 0.816), continuous renal replacement therapy (adjusted OR, 1.36; 95% CI, 0.56 to 3.28; p = 0.495) and resternotomy for postoperative bleeding (adjusted OR, 1.55; 95% CI, 0.55 to 4.30; p = 0.405). No difference was found in postoperative ventilation time (adjusted B, -1.45; SE, 2.33; p = 0.535), length of intensive care unit stay (adjusted B, -0.12; SE, 0.25; p = 0.633) and length of hospital stay (adjusted B, 0.48; SE, 0.58; p = 0.408).Based on the 5-year experience of TXA administration in cardiac surgery with CPB, we found that postoperative stroke was associated with intraoperative TXA administration in patients undergoing cardiac surgery, especially in those undergoing valve surgeries only. This study may suggest that TXA should be administrated according to clear indications after evaluating the bleeding risk in patients undergoing cardiac surgery, especially in those with high stroke risk.

MicroRNAs (miRNAs) have been widely accepted as a class of gene expression regulators which post-translationally regulate protein expression. These small noncoding RNAs have been proved closely involved in the modulation of various pathobiological processes in cancer. In this research, we demonstrated that miR-148a expression was significantly down-regulated in gastric cancer tissues in comparison with the matched normal mucosal tissues, and its expression was statistically associated with lymph node metastasis. Ectopic expression of miR-148a inhibited tumor cell proliferation and migration in vitro, and inhibited tumor formation in vivo. Subsequently, we identified cholecystokinin B receptor (CCK-BR) as a direct target of miR-148a using western blot and luciferase activity assay. More importantly, siRNA-induced knockdown of CCK-BR elicited similar anti-oncogenic effects (decreased proliferation and migration) as those induced by enforced miR-148a expression. We also found that miR-148a-mediated anti-cancer effects are dependent on the inhibition of STAT3 and Akt activation, which subsequently regulates the pathways involved in cell proliferation and migration. Taken together, our results suggest that miR-148a serves as a tumor suppressor in human gastric carcinogenesis by targeting CCK-BR via inactivating STAT3 and Akt.

Recent studies have demonstrated that the central dopaminergic system is implicated in the mechanism underlying general anesthesia. Here, we investigated whether dopaminergic ventral tegmental area (VTA) neurons participate in general anesthesia. Dopaminergic VTA neurons were selectively ablated from male Sprague Dawley rats via the bilateral infusion of 6-hydroxydopamine (6-OHDA) into the VTA. Two weeks after infusion, the number of dopaminergic neurons in the bilateral VTA was markedly reduced in the 6-OHDA-treated rats compared with the vehicle-treated rats. These bilateral VTA lesions significantly prolonged the recovery time for propofol but did not significantly alter its onset time or 50% effective dose (ED50) value. In addition, the anesthetic responses to isoflurane and ketamine were unaffected by the VTA lesions. Our findings suggested that dopaminergic VTA neurons might be involved in the emergence from propofol anesthesia.

Intraoperative blood salvage, an effective blood conservation strategy, has not been applied in onco-surgery, because of potential malignant cell contamination. In this study we tested effectiveness of a modified leukocyte depletion filter (M-LDF) for removal of tumor cells.The effects of M-LDF and regular LDF on removal of cells (HepG2 cell line) were compared. The safety of M-LDF was tested with blood (collected and washed during onco-surgery), the salvaged blood mixed with tumor cells from the solid tumor of the same patient, or mixed with HepG2 cells (n=30 in each protocol). Cancer cells were identified by flow cytometry, culture and bioassay with and without filtration.M-LDF removed 5-log of HepG2 and nucleated cells, which was much higher than regular LDF, and cells were destroyed when they passed through M-LDF. Cytokeratin-positive cells in all samples were removed by M-LDF. Invasive growth adherent cells were found in most of unfiltered samples and 67% of the inoculated nude mice developed tumors in LDF-treated sample. Neither adherent cells nor nude mice developed tumors were found in M-LDF-treated samples.Since M-LDF can effectively remove and destroy cancer cells in the salvaged blood, it has great potential for clinical application.

An understanding of how to safely apply intraoperative blood salvage (IBS) in cancer surgery has not yet been obtained. Here, we investigated the optimal dose of 137Cs gamma-ray irradiation for killing human hepatocarcinoma (HepG2), gastrocarcinoma (SGC7901), and colonic carcinoma (SW620) tumor cells while preserving co-cultured erythrocytes obtained from 14 healthy adult volunteers. HepG2, SGC7901, or SW620 cells were mixed into the aliquots of erythrocytes. After the mixed cells were treated with 137Cs gamma-ray irradiation (30, 50, and 100 Gy), tumor cells and erythrocytes were separated by density gradient centrifugation in Percoll with a density of 1.063 g/ml. The viability, clonogenicity, DNA synthesis, tumorigenicity, and apoptosis of the tumor cells were determined by MTT assay, plate colony formation, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, subcutaneous xenograft implantation into immunocompromised mice, and annexin V/7-AAD staining, respectively. The ATP concentration, 2,3-DPG level, free Hb concentration, osmotic fragility, membrane phosphatidylserine externalization, blood gas variables, reactive oxygen species levels, and superoxide dismutase levels in erythrocytes were analyzed. We found that 137Cs gamma-ray irradiation at 50 Gy effectively inhibited the viability, proliferation, and tumorigenicity of HepG2, SGC7901, and SW620 cells without markedly damaging the oxygen-carrying ability or membrane integrity or increasing the oxidative stress of erythrocytes in vitro. These results demonstrated that 50 Gy irradiation in a standard 137Cs blood irradiator might be a safe and effective method of inactivating HepG2, SGC7901, and SW620 cells mixed with erythrocytes, which might help to safely allow IBS in cancer surgery.

To explore the patterns of gene expression in gastric cancer, a total of 26 paired gastric cancer and noncancerous tissues from patients were enrolled for gene expression microarray analyses. Limma methods were applied to analyze the data, and genes were considered to be significantly differentially expressed if the False Discovery Rate (FDR) value was < 0.01, P-value was 2. Subsequently, Gene Ontology (GO) categories were used to analyze the main functions of the differentially expressed genes. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we found pathways significantly associated with the differential genes. Gene-Act network and co-expression network were built respectively based on the relationships among the genes, proteins and compounds in the database. 2371 mRNAs and 350 lncRNAs considered as significantly differentially expressed genes were selected for the further analysis. The GO categories, pathway analyses and the Gene-Act network showed a consistent result that up-regulated genes were responsible for tumorigenesis, migration, angiogenesis and microenvironment formation, while down-regulated genes were involved in metabolism. These results of this study provide some novel findings on coding RNAs, lncRNAs, pathways and the co-expression network in gastric cancer which will be useful to guide further investigation and target therapy for this disease.

Overexpressed CEACAM6 in tumor tissues plays important roles in invasion, metastasis and anoikis resistance in a variety of human cancers. We recently reported that CEACAM6 expression is upregulated in Gastric cancer (GC) tissues and promoted GC metastasis. Here, we report that CEACAM6 promotes peritoneal metastases in vivo and is negatively correlated with E-cadherin expression in GC tissues. Overexpressed CEACAM6 induced epithelial-mesenchymal transition (EMT) in GC, as measured by increases in the EMT markers N-cadherin, Vimentin and Slug while E-cadherin expression was decreased in CEACAM6-overexpressing GC cells; opposing results were observed in CEACAM6-silenced cells. Furthermore, E-cadherin expression was negatively correlated with depth of tumor invasion, lymph node metastasis and TNM stage in GC tissues. Additionally, CEACAM6 elevated matrix metalloproteinase-9 (MMP-9) activity in GC, and anti-MMP-9 antibody could reverse the increasing invasion and migration induced by CEACAM6. CEACAM6 also increased the levels of phosphorylated AKT, which is involved in the progression of a variety of human tumors. We further observed that LY294002, a PI3K inhibitor, could reverse CEACAM6-induced EMT via mesenchymal-epithelial transition. These findings suggest that CEACAM6 enhances invasion and metastasis in GC by promoting EMT via the PI3K/AKT signaling pathway.

PURPOSE: Activation of Toll like receptors (TLRs) signaling has been implicated in promoting malignant cell invasion and metastatic potential. Previously we demonstrated that increased TLR-9 expression predicted poor survival in oral cancer patients. The objective of this study is to further investigate the roles and potential molecular mechanisms of TLR-9 signaling in human oral cancer cell invasion. METHODS: Cell migration, invasion and protein expression were detected by wound healing assay, Transwell chambers model and western blot. The secretion and activity levels of metalloproteinases-2/9 were quantified by ELISA and Gelatin zymography. EMSA and ChIP assays were employed to detect the activity of AP-1signal pathway. TLR-9 siRNA transfection was used to regulate the expression and activity of TLR-9 in oral cancer cell line HB cells. RESULT: The results of both wound healing assay and in vitro Transwell assay revealed that activation of TLR-9 induced dose- and time- dependent migration and invasion of HB cells. An increased expression, secretion and activity of MMP-2 were observed upon the treatment of CpG-ODN. The TLR-9 signaling-mediated MMP-2 expression appeared to be a consequence of AP-1 activation, because that their DNA binding activity was enhanced by CpG-ODN treatment. All these influences were efficiently repressed by the knockdown of TLR-9 through siRNA or pretreatment of an AP-1 inhibitor. CONCLUSION: Activation of TLR-9 signaling could promote human oral cancer HB cells invasion with the induction of MMP-2 presentation by attenuating AP-1 binding activity, suggesting a novel anti-metastatic application for TLR-9 targeted therapy in oral cancer in the future.

A major challenge in the treatment of pancreatic ductal adenocarcinoma is the failure of chemotherapy, which is likely due to the presence of the cancer stem cells (CSCs).To identify side population (SP) cells and characterize s-like properties in human pancreatic cancer cell lines (h-PCCLs) and to exploit the efficacy of concomitant targeting of multiple key transcription factors governing the stemness of pancreatic CSCs in suppressing CSC-like phenotypes.Flow cytometry and Hoechst 33342 DNA-binding dye efflux assay were used to sort SP and non-SP (NSP) cells from three h-PCCLs: PANC-1, SW1990, and BxPc-3. The self-renewal ability, invasiveness, migration and drug resistance of SP cells were evaluated. Expression of CSC marker genes was analyzed. Tumorigenicity was assessed using a xenograft model in nude mice. Effects of a complex decoy oligonucleotide (cdODN-SCO) designed to simultaneously targeting Sox2, Oct4 and c-Myc were assessed.CSCs were enriched in the side proportion (SP) cells contained in the h-PCCLs and they possessed aggressive growth, invasion, migration and drug-resistance properties, compared with NSP cells. SP cells overexpressed stem cell markers CD133 and ALDH1, pluripotency maintaining factors Nanog, Sox2 and Oct4, oncogenic transcription factor c-Myc, signaling molecule Notch1, and drug resistant gene ABCG2. Moreover, SP cells consistently demonstrated significantly greater tumorigenicity than NSP cells in xenograft model of nude mice. CdODN-SOC efficiently suppressed all CSC properties and phenotypes, and minimized the tumorigenic capability of the SP cells and the resistance to chemotherapy. By comparison, the negative control failed to do so.The findings indicate that targeting the key genes conferring the stemness of CSCs can efficiently eliminate CSC-like phenotypes, and thus may be considered a new approach for cancer therapy. Specifically, the present study establishes the combination of Sox2/Oct4/c-Myc targeting as a potential anti-pancreatic cancer agent worthy of further studies in preclinical settings.

Trastuzumab has been approved for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric and gastroesophageal junction cancers (GC and GJC) in combination with chemotherapy. The aim of this HER2 early/advanced gastric epidemiology (HER-EAGLE) study was to evaluate the frequency of HER2 over-expression and to evaluate agreement on HER2 status assessment in GC and GJC patients in local laboratories versus a central laboratory in China. Tumor samples from 734 GC or GJC patients who were enrolled at 11 different hospitals in China were examined. HER2 status was assessed by immunohistochemistry (IHC), and followed by dual-color silver-enhanced in Situ hybridization (DSISH) in IHC 2+ cases. Clinicopathologic characteristics were collected from all of the patients. HER2-positive tumors were identified in 12.0% (88/734) of the GC and GJC cases. There were significantly higher rates of HER2 positivity in patients with GJC (GJC: 18.1%, GC: 9.7%, P=0.002), and intestinal-type cancers using the Lauren classification (intestinal: 23.6%, diffuse/mixed: 4.3%, P

Recent studies have demonstrated that volatile anesthetic postconditioning confers myocardial protection against ischemia-reperfusion (IR) injury through activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has been shown to be impaired in hypercholesterolemia. Therefore, we investigate whether anesthetic-induced cardiac protection was maintained in hypercholesterolemic rats. In the present study, normocholesteolemic or hypercholesterolemic rat hearts were subjected to 30 min of ischemia and 2 h of reperfusion. Animals received 2.4% sevoflurane for 5 min or 3 cycles of 10-s ischemia/10-s reperfusion. The hemodynamic parameters, including left ventricular developed pressure, left ventricular end-diastolic pressure and heart rate, were continuously monitored. The infarct size, apoptosis, p-Akt, p-ERK1/2, p-GSK3β were determined. We found that both sevoflurane and ischemic postconditioning significantly improved heart pump function, reduced infarct size and increased the phosphorylation of Akt, ERK1/2 and their downstream target of GSK3β in the healthy rats. In the hypercholesterolemic rats, neither sevoflurane nor ischemic postconditioning improved left ventricular hemodynamics, reduced infarct size and increased the phosphorylated Akt, ERK1/2 and GSK3β. In contrast, GSK inhibitor SB216763 conferred cardioprotection against IR injury in healthy and hypercholesterolemic hearts. In conclusions, hyperchoesterolemia abrogated sevoflurane-induced cardioprotection against IR injury by alteration of upstream signaling of GSK3β and acute GSK inhibition may provide a novel therapeutic strategy to protect hypercholesterolemic hearts against IR injury.

MicroRNA has been recently recognized as playing a prominent role in tumorigenesis and metastasis. Here, we report that miR-338-3p was epigenetically silenced in gastric cancer, and its down-regulation was significantly correlated with gastric cancer clinicopathological features. Strikingly, restoring miR-338-3p expression in SGC-7901 gastric cancer cells inhibited proliferation, migration, invasion and tumorigenicity in vitro and in vivo, at least partly through inducing apoptosis. Furthermore, we demonstrate the oncogene SSX2IP is a target of miR-338-3p. We propose that miR-338-3p functions as a tumor suppressor in gastric cancer, and the methylation status of its CpG island could serve as a potential diagnostic marker for gastric cancer.

The Shigella flexneri IcsA (VirG) protein is a polarly distributed outer membrane protein that is a fundamental virulence factor which interacts with neural Wiskott-Aldrich syndrome protein (N-WASP). The activated N-WASP then activates the Arp2/3 complex which initiates de novo actin nucleation and polymerisation to form F-actin comet tails and allows bacterial cell-to-cell spreading. In a previous study, IcsA was found to have three N-WASP interacting regions (IRs): IR I (aa 185-312), IR II (aa 330-382) and IR III (aa 508-730). The aim of this study was to more clearly define N-WASP interacting regions II and III by site-directed mutagenesis of specific amino acids. Mutant IcsA proteins were expressed in both smooth lipopolysaccharide (S-LPS) and rough LPS (R-LPS) S. flexneri strains and characterised for IcsA production level, N-WASP recruitment and F-actin comet tail formation. We have successfully identified new amino acids involved in N-WASP recruitment within different N-WASP interacting regions, and report for the first time using co-expression of mutant IcsA proteins, that N-WASP activation involves interactions with different regions on different IcsA molecules as shown by Arp3 recruitment. In addition, our findings suggest that autochaperone (AC) mutant protein production was not rescued by another AC region provided in trans, differing to that reported for two other autotransporters, PrtS and BrkA autotransporters.

Emerging studies have indicated that microRNAs are involved in the development and progression of cancer. Here we found that miR-202-3p was frequently down-regulated in gastric cancer tissues. Overexpression of miR-202-3p in gastric cancer cells MKN-28 and BGC-823, markedly suppressed cell proliferation and induced cell apoptosis both in vitro and in vivo. Furthermore, Gli1 expression was frequently positive in gastric cancer tissues and inversely correlated with miR-133b expression. We demonstrate that the transcriptional factor Gli1 was a target of miR-202-3p and plays an essential role as a mediator of the biological effects of miR-202-3p in gastric cancer. MiR-202-3p also inhibited the expression of γ-catenin and BCL-2. Taken together, these findings suggest that miR-202-3p may function as a novel tumor suppressor in gastric cancer and its anti-tumor activity may attribute the direct targeting and inhibition of Gli1.

Elderly patients are more likely to suffer from postoperative memory impairment for volatile anesthetics could induce aging neurons degeneration and apoptosis while the mechanism was still elusive. Therefore we hypothesized that ER stress mediated hippocampal neurons apoptosis might play an important role in the mechanism of sevoflurane-induced cognitive impairment in aged rats. Thirty 18-month-old male Sprague-Dawley rats were divided into two groups: the sham anesthesia group (exposure to simply humidified 30-50% O2 balanced by N2 in an acrylic anesthetizing chamber for 5 hours) and the sevoflurane anesthesia group (received 2% sevoflurane in the same humidified mixed air in an identical chamber for the same time). Spatial memory of rats was assayed by the Morris water maze test. The ultrastructure of the hippocampus was observed by transmission electron microscopy (TEM). The expressions of C/EBP homologous protein (CHOP) and caspase-12 in the hippocampus were observed by immunohistochemistry and real-time PCR analysis. The apoptosis neurons were also assessed by TUNEL assay. The Morris water maze test showed that sevoflurane anesthesia induced spatial memory impairment in aging rats (P

hUC-MSCs hold great promise in vitro neuronal differentiation and therapy for neurodegenerative disorders including Parkinson's disease. Recent studies provided that Lmx1α play an important role in the midbrain dopamine cells differentiation. Neurturin is desired candidate gene for providing a neuroprotective to DA neurons. In this study, we investigated a novel neuronal differentiation strategy in vitro with Lmx1α and NTN. We transferred these two genes to hUC-MSCs by recombinant adenovirus combined with Lmx1α regulatory factor and other inductor to improve the efficiency of inducing. Then those induced cells were implanted into the striatum and substantia nigra of MPTP lesioned hemi-parkinsonian rhesus monkeys. Monkeys were monitored by using behavioral test for six months after implantation. The result showed that cells isolated from the umbilical cord were negative for CD45, CD34 and HLA-DR, but were positive for CD44, CD49d, CD29. After those cells were infected with recombinant adenovirus, RT-PCR result shows that both Lmx1α and NTN genes were transcribed in hUC-MSCs. We also observed that the exogenous were highly expressed in hUC-MSCs from immunofluorescence and western blot. Experiments in vitro have proved that secretion NTN could maintain the survival of rat fetal midbrain dopaminergic neurons. After hUC-MSCs were induced with endogenous and exogenous factors, the mature neurons specific gene TH, Pitx3 was transcripted and the neurons specific protein TH, β-tubulinIII, NSE, Nestin, MAP-2 was expressed in those differentiated cells. In addition, the PD monkeys, transplanted with the induced cells demonstrated the animals' symptoms amelioration by the behavioral measures. Further more, pathological and immunohistochemistry data showed that there were neuronal-like cells survived in the right brain of those PD monkeys, which may play a role as dopaminergic neurons. The findings from this study may help us to better understand the inside mechanisms of PD pathogenesis and may also help developing effective therapy for Parkinson's disease.

The objective of this work is to investigate the relationship between endo-β-mannanase and leaf abscission, and response to wounding in soybean (Glycine max). An endo-β-mannanase gene GmMAN1 was cloned from the abscission zone in petiole explants, and was heterologously expressed in E. coli. Polyclonal antibodies were raised against the fusion protein. The increases in activity, isoform numbers, and amounts of transcripts and proteins of GmMAN1 were found not only in the abscission zone but also in the non-abscission zone during petiole abscission in the explants, but not in these two tissues during leaf abscission artificially induced by ethephon treatment in the intact plants. The changes in endo-β-mannanase expression patterns in these two tissues were probably induced by the inherent mechanical wounding during the preparation of explants. When soybean plants were wounded by removing half of the leaf blade of the first pair of true leaves, the transcripts and proteins of GmMAN1 were induced in the leaves and stem, leading to the increases in enzyme activity and isoform numbers in them. It is concluded that the soybean endo-β-mannanase GmMAN1 is not associated with leaf abscission, but might be involved in the response to wounding.

There is accumulating evidence to implicate the importance of EphBs receptors and ephrinBs ligands were involved in modulation of spinal nociceptive information. However, the downstream mechanisms that control this process are not well understood. In the present study, we investigated whether phosphatidylinositol 3-kinase (PI3K), as the downstream effectors, participates in modulation of spinal nociceptive information related to ephrinBs/EphBs. Intrathecal injection of ephrinB1-Fc produced a dose- and time-dependent thermal and mechanical hyperalgesia, accompanied by the increase of spinal PI3K-p110γ, phosphorylation of AKT (p-AKT) and c-Fos expression. Pre-treatment with PI3K inhibitor wortmannin or LY294002 prevented activation of spinal AKT induced by ephrinB1-Fc. Inhibition of spinal PI3K signaling dose-dependently prevented and reversed pain behaviors and spinal c-Fos protein expression induced by intrathecal injection of ephrinB1-Fc. Inhibition of EphBs receptors by intrathecal injection of EphB1-Fc reduced formalin-induced inflammation and chronic constrictive injury-induced neuropathic pain behaviors accompanied by decreased expression of spinal PI3K,p-AKT and c-Fos protein. Furthermore, pre-treatment with PI3K inhibitor wortmannin or LY294002 prevented ephrinB1-Fc-induced ERK activation in spinal. These data demonstrated that PI3K and PI3K crosstalk to ERK signaling contributed to modulation of spinal nociceptive information related to ephrinBs/EphBs.

ObjectiveTo evaluate the effects of Tai Chi in the treatment of patients with chronic low back pain by Meta-analysis and to investigate its influencing factors.MethodsThe study searched eight databases (PubMed, Embase, The Cochrane Library, Web of Science, China Knowledge Network, Wanfang, VIP, and CBM) from inception to October 2023. Two investigators independently selected 10 eligible randomized controlled trials (RCT) against inclusion and exclusion criteria, followed by data extraction and study quality assessment by ROB 2. The outcomes of interest were pain intensity and disability. The studies were combined using meta-analysis when statistical pooling of data was possible. The quality of the evidence was assessed using the GRADE approach.Results10 randomized controlled studies with a total sample of 886 cases were included, of which 4 (40%) were assessed as low risk of bias. The effect size of Tai Chi for chronic low back pain was [Weighted Mean Difference (WMD) with 95% Confidence Interval (CI) = -1.09 (-1.26, -0.92), p < 0.01], all achieving large effect sizes and statistically significant; the effect size for disability was [Standard Mean Difference (SMD) with 95% CI = -1.75 (-2.02, -1.48), p < 0.01], and the combined effect sizes of physical health and mental health for quality of life were [WMD (95% CI) = 4.18 (3.41, 4.95), p < 0.01; WMD (95% CI) = 3.23 (2.42, 4.04), p < 0.01] respectively. The incidence of adverse reactions was low. Meta regression and subgroup analysis showed that there was no significant effect on intervention measures (Tai Chi alone, Tai Chi as additional therapy, water Tai Chi), Tai Chi school (Chen and Yang) and the number of total intervention sessions (> 30 and ≤ 30). The evidence quality evaluation showed that the evidence of pain, physical health of quality of life and mental health score was medium quality, while the evidence of disability and adverse reactions was low quality.ConclusionsTai Chi has an obvious effect of in relieving chronic low back pain. Tai Chi alone and Tai Chi as supplementary therapy have good effects. Tai Chi in water have not been verified. Chen style Tai Chi and Yang's Tai Chi, intervention more than 30 times or less than 30 times had no significant difference in the effect of intervention on CLBP.

BackgroundThe China-Myanmar border area is considered a hot spot of active HIV-1 recombination in Southeast Asia. To better understand the characteristics of HIV-1 transmission in this area, a cross-sectional HIV-1 molecular epidemiological survey was conducted in Baoshan Prefecture of Yunnan Province.MethodsIn total, 708 newly reported HIV-1 cases in Baoshan Prefecture from 2019 to 2020 were included in this study. HIV-1 gag, pol and env genes were sequenced, and the spatial and demographic distributions of HIV-1 genotypes were analyzed. The characteristics of HIV-1 transmission were investigated using the HIV-1 molecular network method.ResultsIn the 497 samples with genotyping results, 19 HIV-1 genotypes were found, with URFs being the predominant strains (30.2%, 150/497). The main circulating HIV-1 strains were mostly distributed in the northern area of Baoshan. URFs were more likely identified in Burmese individuals, intravenous drug users and those younger than 50 years old. CRF08_BC was more likely detected in farmers and those of Han ethnicity, CRF01_AE in the young and those of Han ethnicity, and CRF07_BC in the subpopulation with junior middle school education and higher. Moreover, CRF118_BC and CRF64_BC were more likely found in the subpopulation aged ≥40 years and ≥50 years, respectively. Among 480 individuals with pol sequence detection, 179 (37.3%) were grouped into 78 clusters, with Baoshan natives being more likely to be in the network. The proportion of the linked individuals showed significant differences when stratified by the regional origin, marital status, age and county of case reporting. In the molecular network, recent infections were more likely to occur among nonfarmers and individuals aged below 30 years.ConclusionsHIV-1 genetics has become complex in Baoshan. HIV-1 molecular network analysis provided transmission characteristics in the local area, and these findings provided information to prioritize transmission-reduction interventions.

The sulfonylurea herbicide nicosulfuron is efficient, harmless and selective at low doses and has been widely used in maize cultivation. In this study, a pair of corn sister lines, HK301 (nicosulfuron-tolerence, NT) and HK320 (nicosulfuron-sensitive, NS), was chosen to study the effect of nicosulfuron on plant growth and sugar metabolism in sweet maize (Zea mays L.) seedlings. All the experimental samples were subjected to treatment with water or 80 mg kg-1 of nicosulfuron when the sweet maize seedlings grew to the four-leaf stage. Nicosulfuron significantly inhibited the growth of NS line. The content of sucrose and the activities of sucrose phosphate synthase and sucrose synthase in the two inbred lines increased differentially under nicosulfuron stress compared with the respective control treatment. After nicosulfuron treatment, the activities of hexokinase and 6-phosphofructokinase and the contents of pyruvic acid and citric acid in NS line decreased significantly compared with those of NT line, while the content of sucrose and activities of sucrose phosphate synthase and sucrose synthase increased significantly. The disruption of sugar metabolism in NS line led to a lower supply of energy for growth. This study showed that the glycolysis pathway and the tricarboxylic acid cycle were enhanced in nicosulfuron-tolerant line under nicosulfuron stress in enhancing the adaptability of sweet maize.

Viral nervous necrosis (VNN) is an acute and serious fish disease caused by nervous necrosis virus (NNV) which has been reported massive mortality in more than fifty teleost species worldwide. VNN causes damage of necrosis and vacuolation to central nervous system (CNS) cells in fish. It is difficult to identify the specific type of cell targeted by NNV, and to decipher the host immune response because of the functional diversity and highly complex anatomical and cellular composition of the CNS. In this study, we found that the red spotted grouper NNV (RGNNV) mainly attacked the midbrain of orange-spotted grouper (Epinephelus coioides). We conducted single-cell RNA-seq analysis of the midbrain of healthy and RGNNV-infected fish and identified 35 transcriptionally distinct cell subtypes, including 28 neuronal and 7 non-neuronal cell types. An evaluation of the subpopulations of immune cells revealed that macrophages were enriched in RGNNV-infected fish, and the transcriptional profiles of macrophages indicated an acute cytokine and inflammatory response. Unsupervised pseudotime analysis of immune cells showed that microglia transformed into M1-type activated macrophages to produce cytokines to reduce the damage to nerve tissue caused by the virus. We also found that RGNNV targeted neuronal cell types was GLU1 and GLU3, and we found that the key genes and pathways by which causes cell cytoplasmic vacuoles and autophagy significant enrichment, this may be the major route viruses cause cell death. These data provided a comprehensive transcriptional perspective of the grouper midbrain and the basis for further research on how viruses infect the teleost CNS.

Background & aimThe coronavirus disease 2019 (COVID-19) pandemic has affected the life and work of people worldwide. The present study aimed to evaluate the rhythm disruptions of life, work, and entertainment, and their associations with the psychological impacts during the initial phase of the COVID-19 pandemic.MethodA cross-sectional study was conducted from the 10th to 17th March 2020 in China. A structured e-questionnaire containing general information, the Chinese version of Brief Social Rhythm Scale, and Zung's self-rating scales of depression and anxiety (SDS and SAS) was posted and collected online through a public media (i.e. EQxiu online questionnaire platform). Scores in sleeping, getting up, and socializing (SGS) rhythm and eating, physical practice, and entertainment (EPE) rhythm were compared among and between participants with different sociodemographic backgrounds including gender, age, education, current occupation, annual income, health status, and chronic disease status. Correlations of SDS and SAS with SGS-scale and EPE-scale were also analyzed.ResultsOverall, 5854 participants were included. There were significant differences in the scores of SGS-scale and EPE-scale among people with different sociodemographic backgrounds. The scores were significantly higher in the groups with female gender, low education level, lower or higher than average income, poor health status, ages of 26-30 years or older than 61 years, nurses and subjects with divorce or widow status. There were also significant differences in SAS and SDS scores among people with different sociodemographic backgrounds (all P< 0.05). The overall prevalence of depression and anxiety was 24.3% and 12.6%, respectively, with nurses having the highest rates of depression (32.94%) and anxiety (18.98%) among the different occupational groups. SGS-scale was moderately correlated with SDS and SAS, and disruption of SGS rhythm was an independent risk factor for depression and anxiety.ConclusionSocial rhythm disruption was independently associated with depression and anxiety. Interventions should be applied to people vulnerable to the rhythm disruption during the COVID-19 pandemic.

Tail adipose as one of the important functional tissues can enhance hazardous environments tolerance for sheep. The objective of this study was to gain insight into the underlying development mechanisms of this trait. A quantitative analysis of protein abundance in ovine tail/rump adipose tissue was performed between Chinese local fat- (Kazakh, Hu and Lanzhou) and thin-tailed (Alpine Merino, Tibetan) sheep in the present study by using lable-free approach. Results showed that 3400 proteins were identified in the five breeds, and 804 were differentially expressed proteins, including 638 up regulated proteins and 83 down regulated proteins in the tail adipose tissues between fat- and thin-tailed sheep, and 8 clusters were distinguished for all the DEPs' expression patterns. The differentially expressed proteins are mainly associated with metabolism pathways and peroxisome proliferator activated receptor signaling pathway. Furthermore, the proteomics results were validated by quantitative real-time PCR and Western Blot. Our research has also suggested that the up-regulated proteins ACSL1, HSD17β4, FABP4 in the tail adipose tissue might contribute to tail fat deposition by facilitating the proliferation of adipocytes and fat accumulation in tail/rump of sheep. Particularly, FABP4 highly expressed in the fat-tail will play an important role for tail fat deposition. Our study might provide a novel view to understanding fat accumulation in special parts of the body in sheep and other animals.

Pollen wall consists of several complex layers which form elaborate species-specific patterns. In Arabidopsis, the transcription factor ABORTED MICROSPORE (AMS) is a master regulator of exine formation, and another transcription factor, TRANSPOSABLE ELEMENT SILENCING VIA AT-HOOK (TEK), specifies formation of the nexine layer. However, knowledge regarding the temporal regulatory roles of TEK in pollen wall development is limited. Here, TEK-GFP driven by the AMS promoter was prematurely expressed in the tapetal nuclei, leading to complete male sterility in the pAMS:TEK-GFP (pat) transgenic lines with the wild-type background. Cytological observations in the pat anthers showed impaired callose synthesis and aberrant exine patterning. CALLOSE SYNTHASE5 (CalS5) is required for callose synthesis, and expression of CalS5 in pat plants was significantly reduced. We demonstrated that TEK negatively regulates CalS5 expression after the tetrad stage in wild-type anthers and further discovered that premature TEK-GFP in pat directly represses CalS5 expression through histone modification. Our findings show that TEK flexibly mediates its different functions via different temporal regulation, revealing that the temporal regulation of TEK is essential for exine patterning. Moreover, the result that the repression of CalS5 by TEK after the tetrad stage coincides with the timing of callose wall dissolution suggests that tapetum utilizes temporal regulation of genes to stop callose wall synthesis, which, together with the activation of callase activity, achieves microspore release and pollen wall patterning.

OBJECTIVES:Fluctuation is a common but neglected phenomenon of physical activity (PA) behavior. This study aimed to explore the psychosocial profiles of PA fluctuation in office employees, and to examine the association of latent profiles with demographics and PA level. METHOD:434 Chinese office employees who were identified as PA fluctuators (M = 32.4 years, SD = 6.9, 55.5% female) completed a cross-sectional online survey covering demographics, PA behavior, and six psychosocial indicators (self-efficacy, planning, action control, affective attitude, social support, and perceived barriers). Latent profile analysis was used to determine PA fluctuators' psychosocial profiles. Associated factors of profile membership were identified with multinomial logistic regression. RESULTS:The two-profile model (uncommitted vs. moderately committed) was selected as the best solution. The moderately committed group (n = 346, 79.7%) possessed a more active mindset by reporting significantly higher scores of self-efficacy (t = 9.42 p < .001), planning (t = 16.33 p < .001), action control (t = 14.55 p < .001), affective attitude (t = 13.33 p < .001), and social support (t = 11.50 p < .001) compared with the uncommitted group (n = 88, 20.3%). Results from a multinomial logistic regression showed that the moderately committed profile was associated with normal weight status (OR = 2.00, p< .05), having a medium managerial position (OR = 2.54, p< .01), and high level of moderate to vigorous PA behavior (OR = 4.85, p< .001). CONCLUSIONS:These findings demonstrate the variability of PA fluctuators' mindsets. Future tailored interventions are recommended to promote PA behavior for this population based on the categorization from the present study.

Myotonia congenita and hypokalemic periodic paralysis type 2 are both rare genetic channelopathies caused by mutations in the CLCN1 gene encoding voltage-gated chloride channel CLC-1 and the SCN4A gene encoding voltage-gated sodium channel Nav1.4. The patients with concomitant mutations in both genes manifested different unique symptoms from mutations in these genes separately. Here, we describe a patient with myotonia and periodic paralysis in a consanguineous marriage pedigree. By using whole-exome sequencing, a novel F306S variant in the CLCN1 gene and a known R222W mutation in the SCN4A gene were identified in the pedigree. Patch clamp analysis revealed that the F306S mutant reduced the opening probability of CLC-1 and chloride conductance. Our study expanded the CLCN1 mutation database. We emphasized the value of whole-exome sequencing for differential diagnosis in atypical myotonic patients.

A new computer-aided detection scheme is proposed, the 3D U-Net convolutional neural network, based on multiscale features of transfer learning to automatically detect pulmonary nodules from the thoracic region containing background and noise. The test results can be used as reference information for doctors to assist in the detection of early lung cancer. The proposed scheme is composed of three major steps: First, the pulmonary parenchyma area is segmented by various methods. Then, the 3D U-Net convolutional neural network model with a multiscale feature structure is built. The network model structure is subsequently fine-tuned by the transfer learning method based on weight, and the optimal parameters are selected in the network model. Finally, datasets are extracted to train the fine-tuned 3D U-Net network model to detect pulmonary nodules. The five-fold cross-validation method is used to obtain the experimental results for the LUNA16 and TIANCHI17 datasets. The experimental results show that the scheme not only has obvious advantages in the detection of medium and large-sized nodules but also has an accuracy rate of more than 70% for the detection of small-sized nodules. The scheme provides automatic and accurate detection of pulmonary nodules that reduces the overfitting rate and training time and improves the efficiency of the algorithm. It can assist doctors in the diagnosis of lung cancer and can be extended to other medical image detection and recognition fields.

ObjectiveTo examine the association of health insurances on catastrophic health expenditure (CHE), and compares that among different health insurances in the last two decades in China.MethodsThe systematic review was conducted according to the Cochrane Handbook and reported according to PRISMA. We searched English and Chinese literature databases including PubMed, EM base, web of science, CNKI, Wan fang, VIP and CBM (Sino Med) for empirical studies on the association between health insurance and CHE from January 2000 to June 2020. Study selection, data extraction and quality appraisal were conducted by two reviewers. The secular trend of CHE rate and comparisons between population with different health insurances were conducted using meta-analysis, subgroup analysis and meta-regression.ResultsA total of 4874 citations were obtained, and finally 30 eligible studies with 633917 participants were included. The overall CHE rate was 13.6% (95% CI: 13.1% - 14.0%) from Jan 2000 to June 2020, 12.8% (95% CI: 12.2% - 13.3%) for people with health insurance compared with 16.2% (95% CI:15.4% - 16.9%) for people without health insurance. For types of insurance, the CHE rate was 13.0% (95% CI: 12.4% - 13.6%) for people with new rural cooperative medical scheme (NCMS), 11.9% (95% CI: 9.3% - 14.5%) for urban employees health insurance (UEBMI), 12.0% (95% CI: 8.3% - 15.6%) for urban residents health insurance (URBMI), and 18.0% (95% CI: - 4.5% - 31.5%) for commercial insurance. However, the CHE rate in China has increased in the past 20 years, even adjusted for other factors. The CHE rate of people with NCMS has increased significantly more than people with UEBMI and URBMI.ConclusionIn the past 20 years, the basic health insurance plan has reduce the rate of CHE to a certain extent, but due to the rapid increase in medical costs and the release of health needs in recent years, it masks the role of health insurance. More efforts are needed to control unreasonable medical demand and rising costs.

Neighborhood relationship plays an important role in spatial analysis, map generalization, co-location data mining and other applications. From the perspective of computation, the formal model of neighborhood representation is a challenging question. This study presents a formal spatial data model for representing the planar spatial field with the support of Delaunay triangulation. Based on the three geometric elements in a triangle of the vertex, edge, and triangle area, the constructed data model describes the spatial objects of a point, line, and region respectively, as well as the neighborhood relationships among them. Three types of operators based on the model are formally defined, expanding, compressing and skeletonizing. For practical applications, three complex operators are extended by continuous and conditional operation. Through the application example of urban building generalization, this study illustrates the analysis of a neighborhood relationship and the detection of spatial conflicts, which is a crucial pre-process during map generalization. With the support of the proposed formal model of neighborhood representation, the generalization method uses the three basic operations of grouping, displacement and aggregation to perform decision making and detailed operation. The generalized result can retain the balance of built-up area better than that of other similar building generalization methods.

Douchi has been consumed as a flavoring ingredient for centuries. During production of douchi, numerous microorganisms play important roles in the hydrolysis and conversion of proteins and starch, which are related to the quality and flavor of the end product. Therefore, in the present study, the microbial diversity in two types of home-made traditional bacterial douchi from Gansu province in northwest China was studied by high-throughput sequencing, and a corresponding analysis of the bacterial and fungal communities were conducted. The results showed that geography may have impacted the fungal diversity and the bacterial and fungal species richness in the samples. The results also showed that the microbial community was significantly different in samples of different origin and the difference in the microbial community at the genus level was greater than at phylum level. Two dominant bacterial genera (Bacillus and Ignatzschineria) were common to the two samples, both of which had a relative abundance of more than 1%. Four bacterial genera (Staphylococcus, Aerococcus, Geobacillus, and Jeotgalicoccus) were dominant only in the sample from Qingyang, while another four (Carnobacterium, Proteus, Aneurinibacillus, and Enterococcus) were dominant only in the sample from Longnan. Two dominant fungal genera (Pichia and Candida) were shared by the two samples. Additionally, two genera (Rhodosporidium and Yarrowia) were dominant only in samples from Longnan. The functional genes of the bacteria present in samples indicated that a significant difference was observed in the bacterial community between samples of different origin. We also found that microbial interactions between bacterial and fungal communities in the samples were very complex. This study provides previously unknown information regarding the impact of the environment on microbial communities in douchi and lays a foundation for further investigations into food ecology in bacterial douchi.